JP5187862B2 - キノリン及びその治療的使用 - Google Patents

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Publication number

JP5187862B2

JP5187862B2 JP2010501594A JP2010501594A JP5187862B2 JP 5187862 B2 JP5187862 B2 JP 5187862B2 JP 2010501594 A JP2010501594 A JP 2010501594A JP 2010501594 A JP2010501594 A JP 2010501594A JP 5187862 B2 JP5187862 B2 JP 5187862B2

Authority

JP

Japan

Prior art keywords

acetic acid

yloxy

difluoromethoxy

chloro

fluoro

Prior art date

2007-04-04

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

Links

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• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title description 8
• 230000001225 therapeutic effect Effects 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 244
• 125000005843 halogen group Chemical group 0.000 claims abstract description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 25
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
• 239000001257 hydrogen Substances 0.000 claims abstract description 24
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 18
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
• 150000002367 halogens Chemical group 0.000 claims abstract description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 8
• 208000006673 asthma Diseases 0.000 claims abstract description 7
• -1 R 3 is methylation Chemical group 0.000 claims description 129
• 150000003839 salts Chemical class 0.000 claims description 28
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 26
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 229910052727 yttrium Inorganic materials 0.000 claims description 18
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 12
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 12
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
• 125000002950 monocyclic group Chemical group 0.000 claims description 11
• 229910052757 nitrogen Inorganic materials 0.000 claims description 11
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 6
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
• 125000006413 ring segment Chemical group 0.000 claims description 6
• CEKCIGRZJPGEKC-UHFFFAOYSA-N 2-[3-[[4-(4-cyclopropylpyrazol-1-yl)phenyl]methyl]-2-(difluoromethoxy)-8-fluoro-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(F)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N(N=C1)C=C1C1CC1 CEKCIGRZJPGEKC-UHFFFAOYSA-N 0.000 claims description 4
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
• 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
• 230000000172 allergic effect Effects 0.000 claims description 4
• 208000028004 allergic respiratory disease Diseases 0.000 claims description 4
• 201000008937 atopic dermatitis Diseases 0.000 claims description 4
• 208000010668 atopic eczema Diseases 0.000 claims description 4
• 125000001072 heteroaryl group Chemical group 0.000 claims description 4
• 206010039083 rhinitis Diseases 0.000 claims description 4
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
• UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical compound C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 claims description 3
• BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 3
• FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 claims description 3
• UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 claims description 3
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 3
• MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 claims description 3
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 3
• MIDBGOVWGDVRNU-UHFFFAOYSA-N 2-[2-(difluoromethoxy)-3-[[4-(2,2-dimethylpropanoyl)phenyl]methyl]-8-fluoro-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(F)C=CC(OCC(O)=O)=C2C(C)=C1CC1=CC=C(C(=O)C(C)(C)C)C=C1 MIDBGOVWGDVRNU-UHFFFAOYSA-N 0.000 claims description 3
• MJYALLQJDQYLFR-UHFFFAOYSA-N 2-[2-cyclopropyl-8-fluoro-4-methyl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-5-yl]oxyacetic acid Chemical compound C1CC1C1=NC2=C(F)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=CC=N1 MJYALLQJDQYLFR-UHFFFAOYSA-N 0.000 claims description 3
• WIBIYJCURGUTMM-UHFFFAOYSA-N 2-[3-[[4-(3-cyclopropylpyrazol-1-yl)phenyl]methyl]-2-(difluoromethoxy)-8-fluoro-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(F)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N(N=1)C=CC=1C1CC1 WIBIYJCURGUTMM-UHFFFAOYSA-N 0.000 claims description 3
• NJAXKCSTUNSYNH-UHFFFAOYSA-N 2-[3-[[4-(5-cyclopropyl-1,2-oxazol-4-yl)phenyl]methyl]-2-(difluoromethoxy)-8-fluoro-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(F)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1C=1C=NOC=1C1CC1 NJAXKCSTUNSYNH-UHFFFAOYSA-N 0.000 claims description 3
• NOTBBHAOPMFKDI-UHFFFAOYSA-N 2-[3-[[4-(5-cyclopropylpyrazol-1-yl)phenyl]methyl]-2-(difluoromethoxy)-8-fluoro-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(F)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1N=CC=C1C1CC1 NOTBBHAOPMFKDI-UHFFFAOYSA-N 0.000 claims description 3
• BLDRWEHEHBTYLZ-UHFFFAOYSA-N 2-[8-chloro-2-(difluoromethoxy)-3-[[4-(2,2-dimethylpropanoyl)phenyl]methyl]-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC1=CC=C(C(=O)C(C)(C)C)C=C1 BLDRWEHEHBTYLZ-UHFFFAOYSA-N 0.000 claims description 3
• XTUPBDFUFDYHGY-UHFFFAOYSA-N 2-[8-chloro-2-(difluoromethoxy)-4-methyl-3-[[4-(1-propan-2-ylpyrazol-3-yl)phenyl]methyl]quinolin-5-yl]oxyacetic acid Chemical compound CC(C)N1C=CC(C=2C=CC(CC=3C(=NC4=C(Cl)C=CC(OCC(O)=O)=C4C=3C)OC(F)F)=CC=2)=N1 XTUPBDFUFDYHGY-UHFFFAOYSA-N 0.000 claims description 3
• VMCZZVGMOXKNMR-UHFFFAOYSA-N 2-[8-chloro-2-(difluoromethoxy)-4-methyl-3-[[4-(1-propan-2-ylpyrazol-4-yl)phenyl]methyl]quinolin-5-yl]oxyacetic acid Chemical compound C1=NN(C(C)C)C=C1C(C=C1)=CC=C1CC1=C(C)C2=C(OCC(O)=O)C=CC(Cl)=C2N=C1OC(F)F VMCZZVGMOXKNMR-UHFFFAOYSA-N 0.000 claims description 3
• PCEWINTZUHCGBM-UHFFFAOYSA-N 2-[8-chloro-2-(difluoromethoxy)-4-methyl-3-[[4-(1h-pyrazol-4-yl)phenyl]methyl]quinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1C=1C=NNC=1 PCEWINTZUHCGBM-UHFFFAOYSA-N 0.000 claims description 3
• WTKMJTZLSNPBHB-UHFFFAOYSA-N 2-[8-chloro-3-[[4-(3-chloropyrazol-1-yl)phenyl]methyl]-2-(difluoromethoxy)-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=CC(Cl)=N1 WTKMJTZLSNPBHB-UHFFFAOYSA-N 0.000 claims description 3
• GNZIHZXAFKMHEX-UHFFFAOYSA-N 2-[8-chloro-3-[[4-(4-chloropyrazol-1-yl)phenyl]methyl]-2-(difluoromethoxy)-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=C(Cl)C=N1 GNZIHZXAFKMHEX-UHFFFAOYSA-N 0.000 claims description 3
• VLYXMBYTYXIUPB-UHFFFAOYSA-N 2-[8-chloro-3-[[4-(4-cyclopropylpyrazol-1-yl)phenyl]methyl]-2-(difluoromethoxy)-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N(N=C1)C=C1C1CC1 VLYXMBYTYXIUPB-UHFFFAOYSA-N 0.000 claims description 3
• OHBBWGBMGOIGLQ-UHFFFAOYSA-N 2-[8-chloro-3-[[4-(5-cyclopropylpyrazol-1-yl)phenyl]methyl]-2-(difluoromethoxy)-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1N=CC=C1C1CC1 OHBBWGBMGOIGLQ-UHFFFAOYSA-N 0.000 claims description 3
• TWYWHVLXPOESPV-UHFFFAOYSA-N 2-[8-fluoro-2-methoxy-4-methyl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-5-yl]oxyacetic acid Chemical compound COC1=NC2=C(F)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=CC=N1 TWYWHVLXPOESPV-UHFFFAOYSA-N 0.000 claims description 3
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 3
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 3
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
• 150000002244 furazanes Chemical class 0.000 claims description 3
• 150000002431 hydrogen Chemical class 0.000 claims description 3
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 3
• 150000003536 tetrazoles Chemical class 0.000 claims description 3
• 229930192474 thiophene Natural products 0.000 claims description 3
• QFAQJJQZCOULEH-INIZCTEOSA-N (2s)-2-[2-cyclopropyl-8-fluoro-4-methyl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-5-yl]oxypropanoic acid Chemical compound C=1C=C(N2N=CC=C2)C=CC=1CC=1C(C)=C2C(O[C@@H](C)C(O)=O)=CC=C(F)C2=NC=1C1CC1 QFAQJJQZCOULEH-INIZCTEOSA-N 0.000 claims description 2
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 2
• YRMNURZYVIBDOY-UHFFFAOYSA-N 2-[2-(difluoromethoxy)-8-fluoro-4-methyl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(F)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=CC=N1 YRMNURZYVIBDOY-UHFFFAOYSA-N 0.000 claims description 2
• QBLZPVQTXZIGEN-UHFFFAOYSA-N 2-[2-(difluoromethoxy)-8-fluoro-4-methyl-3-[[4-(2-propan-2-ylimidazol-1-yl)phenyl]methyl]quinolin-5-yl]oxyacetic acid Chemical compound CC(C)C1=NC=CN1C(C=C1)=CC=C1CC1=C(C)C2=C(OCC(O)=O)C=CC(F)=C2N=C1OC(F)F QBLZPVQTXZIGEN-UHFFFAOYSA-N 0.000 claims description 2
• VATBPDAMEYECHM-UHFFFAOYSA-N 2-[8-chloro-2-(difluoromethoxy)-4-methyl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=CC=N1 VATBPDAMEYECHM-UHFFFAOYSA-N 0.000 claims description 2
• VPAUPWBPMXRBBX-UHFFFAOYSA-N 2-[8-chloro-2-(difluoromethoxy)-4-methyl-3-[[4-(2-propan-2-ylimidazol-1-yl)phenyl]methyl]quinolin-5-yl]oxyacetic acid Chemical compound CC(C)C1=NC=CN1C(C=C1)=CC=C1CC1=C(C)C2=C(OCC(O)=O)C=CC(Cl)=C2N=C1OC(F)F VPAUPWBPMXRBBX-UHFFFAOYSA-N 0.000 claims description 2
• ALUOMCOECKYMKX-UHFFFAOYSA-N 2-[8-chloro-2-methoxy-4-methyl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-5-yl]oxyacetic acid Chemical compound COC1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=CC=N1 ALUOMCOECKYMKX-UHFFFAOYSA-N 0.000 claims description 2
• KARGVHTTWQIJII-UHFFFAOYSA-N 2-[8-chloro-3-[[4-(3-cyclopropylpyrazol-1-yl)phenyl]methyl]-2-(difluoromethoxy)-4-methylquinolin-5-yl]oxyacetic acid Chemical compound FC(F)OC1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N(N=1)C=CC=1C1CC1 KARGVHTTWQIJII-UHFFFAOYSA-N 0.000 claims description 2
• WFELTIRYFWESJZ-UHFFFAOYSA-N 2-[8-chloro-4-methyl-2-propan-2-yl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-5-yl]acetic acid Chemical compound CC(C)C1=NC2=C(Cl)C=CC(CC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=CC=N1 WFELTIRYFWESJZ-UHFFFAOYSA-N 0.000 claims description 2
• NACLEAFCWJZTFP-UHFFFAOYSA-N 2-[8-chloro-4-methyl-2-propan-2-yl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-5-yl]oxyacetic acid Chemical compound CC(C)C1=NC2=C(Cl)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=CC=N1 NACLEAFCWJZTFP-UHFFFAOYSA-N 0.000 claims description 2
• DFBVWPBNNOKBLF-UHFFFAOYSA-N 2-[8-fluoro-4-methyl-2-propan-2-yl-3-[(4-pyrazol-1-ylphenyl)methyl]quinolin-5-yl]oxyacetic acid Chemical compound CC(C)C1=NC2=C(F)C=CC(OCC(O)=O)=C2C(C)=C1CC(C=C1)=CC=C1N1C=CC=N1 DFBVWPBNNOKBLF-UHFFFAOYSA-N 0.000 claims description 2
• 201000004681 Psoriasis Diseases 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 2
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 2
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
• 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims description 2
• 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 2
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
• 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
• 230000011987 methylation Effects 0.000 claims 2
• 238000007069 methylation reaction Methods 0.000 claims 2
• 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims 1
• 108050000258 Prostaglandin D receptors Proteins 0.000 abstract description 22
• 239000003446 ligand Substances 0.000 abstract description 4
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 3
• 102000009389 Prostaglandin D receptors Human genes 0.000 abstract 1
• 238000000034 method Methods 0.000 description 280
• 238000002360 preparation method Methods 0.000 description 248
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 219
• 230000014759 maintenance of location Effects 0.000 description 171
• 239000000203 mixture Substances 0.000 description 170
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 88
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 88
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 68
• KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 66
• 239000000243 solution Substances 0.000 description 65
• 238000005481 NMR spectroscopy Methods 0.000 description 64
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 54
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 51
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 44
• 235000019341 magnesium sulphate Nutrition 0.000 description 44
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 39
• 239000000284 extract Substances 0.000 description 39
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